Combined thermal ablation and liposomal granulocyte-macrophage colony stimulation factor increases immune cell trafficking in a small animal tumor model.

PURPOSE: To characterize intratumoral immune cell trafficking in ablated and synchronous tumors following combined radiofrequency ablation (RFA) and systemic liposomal granulocyte-macrophage colony stimulation factor (lip-GM-CSF). METHODS: Phase I, 72 rats with single subcutaneous R3230 adenocarcinoma were randomized to 6 groups: a) sham; b&c) free or liposomal GM-CSF alone; d) RFA alone; or e&f) combined with blank liposomes or lip-GM-CSF. Animals were sacrificed 3 and 7 days post-RFA. Outcomes included immunohistochemistry of dendritic cells (DCs), M1 and M2 macrophages, T-helper cells (Th1) (CD4+), cytotoxic T- lymphocytes (CTL) (CD8+), T-regulator cells (T-reg) (FoxP3+) and Fas Ligand activated CTLs (Fas-L+) in the periablational rim and untreated index tumor. M1/M2, CD4+/CD8+ and CD8+/FoxP3+ ratios were calculated. Phase II, 40 rats with double tumors were randomized to 4 groups: a) sham, b) RFA, c) RFA-BL and d) RFA-lip-GM-CSF. Synchronous untreated tumors collected at 7d were analyzed similarly. RESULTS: RFA-lip-GMCSF increased periablational M1, CTL and CD8+/FoxP3+ ratio at 3 and 7d, and activated CTLs 7d post-RFA (p<0.05). RFA-lip-GMSCF also increased M2, T-reg, and reduced CD4+/CD8+ 3 and 7d post-RFA respectively (p<0.05). In untreated index tumor, RFA-lip-GMCSF improved DCs, M1, CTLs and activated CTL 7d post-RFA (p<0.05). Furthermore, RFA-lip-GMSCF increased M2 at 3 and 7d, and T-reg 7d post-RFA (p<0.05). In synchronous tumors, RFA-BL and RFA-lip-GM-CSF improved DC, Th1 and CTL infiltration 7d post-RFA. CONCLUSION: Systemic liposomal GM-CSF combined with RFA improves intratumoral immune cell trafficking, specifically populations initiating (DC, M1) and executing (CTL, FasL+) anti-tumor immunity. Moreover, liposomes influence synchronous untreated metastases increasing Th1, CTL and DCs infiltration.

Socio-economic inequity in demand for insecticide-treated nets, in-door residual house spraying, larviciding and fogging in Sudan.

BACKGROUND: In order to optimally prioritize and use public and private budgets for equitable malaria vector control, there is a need to determine the level and determinants of consumer demand for different vector control tools. OBJECTIVES: To determine the demand from people of different socio-economic groups for indoor residual house-spraying (IRHS), insecticide-treated nets (ITNs), larviciding with chemicals (LWC), and space spraying/fogging (SS) and the disease control implications of the result. METHODS: Ratings and levels of willingness-to-pay (WTP) for the vector control tools were determined using a random cross-sectional sample of 720 householdes drawn from two states. WTP was elicited using the bidding game. An asset-based socio-economic status (SES) index was used to explore whether WTP was related to SES of the respondents. RESULTS: IRHS received the highest proportion of highest preferred rating (41.0%) followed by ITNs (23.1%). However, ITNs had the highest mean WTP followed by IRHS, while LWC had the least. The regression analysis showed that SES was positively and statistically significantly related to WTP across the four vector control tools and that the respondents' rating of IRHS and ITNs significantly explained their levels of WTP for the two tools. CONCLUSION: People were willing to pay for all the vector-control tools, but the demand for the vector control tools was related to the SES of the respondents. Hence, it is vital that there are public policies and financing mechanisms to ensure equitable provision and utilisation of vector control tools, as well as protecting the poor from cost-sharing arrangements.